6- and 7-deoxyforskolin and derivatives thereof

Abstract

Novel forskolin derivatives, intermediates and processes for the preparation thereof, and methods for treating cardiac failure and memory deficit utilizing compounds or compositions thereof are disclosed.

We claim: 
     
       1. A compound of formula wherein   R 1  is hydrogen, loweralkyl, arylloweralkyl, a group of formula R 2  R 3  R 4  Si, a group of formula R 5  CO, a group of formula R 8  R 10  N(CHR 11 ) n  CO wherein n is 0 or 1, or Ar';   R 6  is hydrogen, hydroxyl, a group of formula OR 12 , a group of formula OCOR 13 , a group of formula OCONR 14  R 15 , or a group of formula OAr;   R 7  is defined as R 6 , or is a group of formula OCOR 16 , a group of formula OCONR 17  Z, a group of formula OAr', a group of formula OCOAr', a group of formula OCONR 17  Ar', or a group of formula ##STR29## R 6  and R 7  taken together form a group of formula O--C(═S)--O; R 9  is hydrogen;   or R 1  and R 9  maybe taken together to form a group of formula CO, or a group of formula SO or a group of formula CHNR 18  R 19  ;   R 2 , R 3 , and R 4  are the same or not all the same and each is loweralkyl;   R 5  is hydrogen or loweralkyl;   R 8 , R 10  and R 11  are the same or not all the same and each is hydrogen, loweralkyl or arylloweralkyl;   R 8  and R 10  taken together with the nitrogen atom to which they are attached form a group of formula ##STR30##  wherein X is CO, O, S, a group of formula CHR 20  or a group of formula NR 21  ;   R 12  is loweralkyl or alkylaminoloweralkyl;   R 13  is hydrogen, straight or branched chain alkyl containing from 1 to 20 carbon atoms, --CH(OH)CH 2  OH, ##STR31## R 14  is hydrogen, loweralkyl, hydroxyloweralkyl, loweralkoxyloweralkyl, or a group of formula HOCH 2  CH(OH)CH 2  ;   R 15  is hydrogen, hydroxyl, loweralkoxy, loweralkyl, hydroxyloweralkyl, loweralkoxyloweralkyl, loweralkanoyl, loweralkanoylloweralkyl, a group of formula ##STR32##  wherein p is 1 or 2, a group of formula ##STR33##  a group of formula HOCH 2  (OH)CH 2 , a group of formula (CH 2 ) q  NR 22  R 23  wherein q is an integer equalling O or from 2 to 6, a group of formula OR 24  or a group of formula OCOR 25  ;   R 16  is hydroxyloweralkyl, ##STR34##  wherein X is as defined above, a group of formula R 26  OCR 27  R 28  (CH 2 ) r  wherein r is 0, 1, 2 or 3, a group of formula R 29  R 30  N(CH 2 ) s  (CHR 31 )(CH 2 ) s' , wherein s and s' are the same or different and each is 0, 1 or 2, or a group of formula (CH 2 ) f  CO 2  H, wherein f is an integer from 0 through 5;   R 17  is hydrogen or loweralkyl;   R 18  and R 19  are the same or different and each is loweralkyl;   R 18  and R 19  taken together with the nitrogen atom to which they are attached form a group of formula ##STR35##  wherein L is O, S or CHR 20  ; R 20  is hydrogen or loweralkyl;   R 21  is hydrogen or loweralkyl;   R 22  and R 23  are the same or different and each is loweralkyl;   R 22  and R 23  taken together with the nitrogen atom to which they are attached form a group of formula ##STR36##  wherein X is defined as above; R 24  is hydrogen, loweralkyl, a group of formula (CH 2 ) q  NR 22  R 23  wherein R 22 , R 23  and q are as above;   R 25  is hydrogen, loweralkyl, lowercycloalkyl of 3 to 6 carbon atoms, haloloweralkenyl, loweralkanoylloweralkyl, loweralkoxyloweralkyl, loweralkoxycarbonylloweralkyl, loweralkylamino, lowerdialkylamino, a group of formula ##STR37##  wherein p is defined as above, a group of formula ##STR38##  a group of the formula (CH 2 ) q  NR 22  R 23  wherein R 22 , R 23  and q are as defined above, a group of formula ##STR39##  wherein X is as defined above and t is 0 or 1 or a group of formula (CH 2 ) u  N(R 33 )COR 34  wherein u is 1, 2 or 3;   R 26 , R 27  and R 28  are the same or not all the same and each is hydrogen or loweralkyl;   R 29  is hydrogen, loweralkyl, or a group of formula R 35  CO;   R 30  is hydrogen or loweralkyl;   R 29  and R 30  taken together with the nitrogen atom to which they are attached form a group of formula ##STR40##  wherein X is defined above; R 31  is hydrogen, loweralkyl, arylloweralkyl or hydroxyl;   R 33 , R 34  and R 35  are the same or not all the same and each is hydrogen or loweralkyl;   Ar is phenyl, naphthyl, pyridinyl, pyridazinyl or pyrimidinyl, each of which is unsubstituted or mono- or poly-substituted by loweralkyl; halogen or nitro;   Ar' is phenyl, naphthyl, pyridinyl, pyridazinyl, pyrimidinyl, fuanyl, oxazolyl, purinyl or thiazolyl, each of which is unsubstituted or mono- or poly-substituted by loweralkyl, halogen, nitro, or a group of formula NR 34' ,R 35' , or phenyl, naphthyl, pyridinyl or pyrimidinyl, each of which is mono- or poly-substituted by a group of formula NR 34'  R 35' ,;   R 34'   and R 35'   are the same of different and each is hydrogen, loweralkyl or alkylaminoloweralkyl;   R 34'   and R 35'   taken together with the nitrogen atom to which they are attached form a group of formula ##STR41##  wherein M is NR 47 , O or CH 2  and y is 0, 1 or 2 Z is a group of formula (CH 2 ) v  NR 37  R 38  wherein v is 0 or an integer from 2 to 5, a group of formula N═CR 39  R 40  or a group of formula (CH 2 ) g  CO 2  H wherein g is an integer from 0 to 5;   Z and R 17  and the nitrogen to which they are attached form a group ##STR42##  wherein M is NR 47 , O or CH 2  and y is 0, 1 or 2; R 37  and R 38  are the same or different and each is hydrogen, loweralkyl or a group of formula COR 41  ;   R 37  and R 38  taken together with the nitrogen atom to which they are attached form a group of formula ##STR43##  wherein X is defined as above; R 39  is loweralkyl;   R 40  is loweralkyl, loweralkenyl, a group of formula ##STR44##  or a group of formula ##STR45## R 39  and R 40  taken together with the carbon atom to which they are attached form a group of formula ##STR46##  wherein W is O, a group of the formula NR 42 , or a group of formula CHR 43  ;   R 41  is loweralkyl or a group of formula (CH 2 ) x  NR 44  R 45  wherein xi is an integer from 0 to 5;   R 42  is loweralkyl;   R 43  is hydrogen, loweralkyl or a group of formula OR 46  ;   R 44  and R 45  are the same or different and each is loweralkyl;   R 46  is loweralkyl;   R 47  is hydrogen, loweralkyl or (C═O)loweralkyl; and   the optical and geometric isomers thereof, or a pharmaceutically acceptable salt thereof, provided:   (a) if R 6  is hydrogen, then R 7  is not hydrogen;   (b) if R 7  is hydrogen, then R 6  is not hydrogen; and   (c) if neither R 6  nor R 7  is hydrogen then R 6  is OH, R 13  C(═O)O, a group of formula OR 12 , a group of formula OCONR 14  R 15  or a group of formula OAr, R 7  is ##STR47##  or R 6  and R 7  taken together form a group of formula O--C(═S)--O.   
     
     
       2. A compound according to claim 1, wherein R 6  is hydrogen, hydroxyl, a group of formula OCOR 13  or a group of formula OCONR 14  R 15 , R 7  is OAr' wherein Ar' is furanyl, oxazolyl, pyridazinyl, purinyl or thiazolyl, each of which is unsubstituted or mono- or poly-substituted by loweralkyl, halogen, nitro, or a group of formula NR 34'  R 35' , or phenyl, naphthyl, pyridinyl or pyrimidinyl, each of which is mono- or poly-substituted by a group of formula NR 34'  R 35'  ; R 34'   and R 35'   are the same or different and each is hydrogen, loweralkyl or alkyl aminoloweralkyl; and   R 34'   and R 35'   taken together with the nitrogen atom to which they are attached form a group of formula ##STR48##  wherein M and y are defined as in claim 1.   
     
     
       3. A compound according to claim 1, wherein: R 1  is hydrogen;   R 6  is hydrogen, hydroxyl or OCOR 13  ;   R 7  is hydrogen, hydroxyl, OCOR 13 , OCONR 14  R 15 , OCOR 16 , OCONR 17  (CH 2 ) v  NR 37  R 38 , wherein v is an integer from 2 to 5, a group of formula ##STR49##  or OAr' wherein Ar' is phenyl, pyridinyl, pyrimidinyl, pyridazinyl or purinyl, each of which is unsubstituted or mono- or poly-substituted by loweralkyl, halogen, nitro, amino, loweralkylamino, diloweralkylamino, aminoloweralkyl, piperazino, piperidino or morpholino;   R 9  is hydrogen;   R 1  and R 9  taken together form a group of formula CHNR 17  R 18  ; and   R 6  and R 7  taken together form a group of formula O--C(═S)--O.   
     
     
       4. A compound according to claim 3 wherein R 1  and R 9  taken together form a group of formula CHNR 18  R 19 . 
     
     
       5. A compound according to claim 3 wherein R 6  is hydrogen. 
     
     
       6. A compound according to claim 3 wherein R 7  is hydrogen. 
     
     
       7. A compound according to claim 3 wherein R 6  and R 7  taken together form a group of formula O--C(═S)--O. 
     
     
       8. A compound according to claim 3 wherein R 1  and R 6  are hydrogen. 
     
     
       9. The compound of claim 3 which is 7-desacetyl-7-(imidazolothiocarbonyl)forskolin- 1,9-dimethylformamide acetal. 
     
     
       10. The compound of claim 3 which is 7-desacetoxy-7(H)-forskolin-1,9-dimethylformamide acetal. 
     
     
       11. The compound of claim 3 which is 7-desacetylforskolin-1,9-dimethylformamide acetal-6,7-thionocarbonate. 
     
     
       12. The compound of claim 3 which is 6-deoxy-7-desacetoxy-7-hydroxyforskolin-1,9-dimethylformamide acetal. 
     
     
       13. The compound of claim 3 which is 7-desacetoxy-7(H)-forskolin. 
     
     
       14. The compound of claim 3 which is 6-deoxy-7-desacetoxy-7-hydroxyforskolin. 
     
     
       15. The compound of claim 3 which is 6-deoxyforskolin-1,9-dimethylformamide acetal. 
     
     
       16. The compound of claim 3 which is 6-deoxy-7-desacetyl-7-(pyrimidin-2-yl)forskolin-1,9-dimethylformamide acetal. 
     
     
       17. The compound of claim 3 which is 6-deoxyforskolin. 
     
     
       18. The compound of claim 3 which is 6-deoxy-7-desacetyl-7-(pyridin-2-yl)forskolin-1,9-dimethylformamide acetal. 
     
     
       19. The compound of claim 3 which is 6-deoxy-7-desacetyl-7-(pyridin-2-yl)forskolin. 
     
     
       20. The compound of claim 3 which is 6-deoxy-7-desacetyl[[methylamino]carbonyl]forskolin-1,9-dimethylformamide acetal. 
     
     
       21. The compound of claim 3 which is 6-deoxy-7-desacetyl-7-(pyrimidin-2-yl)forskolin. 
     
     
       22. The compound of claim 3 which is 6-acetyl-7-desacetyl-7-imidazolothiocarbonylforskolin-1,9-dimethylformamide acetal. 
     
     
       23. The compound of claim 3 which is 6-deoxy-7-desacetyl[[methylamino]forskolin. 
     
     
       24. The compound of claim 3 which is 6-deoxy-7-desacetyl-7-[[[(3-dimethylamino)-propyl]amino]carbonyl] forskolin-1,9-dimethylformamide acetal. 
     
     
       25. The compound of claim 3 which is 6-acetyl-7-desacetoxy-7(H)-forskolin-1,9-dimethylformamide acetal. 
     
     
       26. The compound of claim 3 which is 6-deoxy-7-desacetyl-7-[[[(3-dimethylamino)propyl]amino]carbonyl] forskolin. 
     
     
       27. The compound of claim 3 which is 6-acetyl-7-desacetoxy-7(H)-forskolin. 
     
     
       28. The compound of claim 3 which is 6-deoxy-7-desacetyl-7-(2-chloropyrimidin-4-yl)forskolin-1,9-dimethylformamide acetal. 
     
     
       29. The compound of claim 3 which is 6-deoxy-7-desacetyl-7-(6-fluoropyridin-2-yl)forskolin-1,9-dimethylformamide acetal. 
     
     
       30. The compound of claim 3 which is 6-deoxy-7-desacetyl-7-(6-fluoropyridin-2-yl)forskolin. 
     
     
       31. The compound of claim 3 which is 6-deoxy-7-desacetyl-7-[6-morpholin-4-yl)pyridin-2-yl]-forskolin. 
     
     
       32. A method for treating cardiac failure in mammals comprising administering to a mammal requiring cardiac failure treatment a cardiac failure treating effective amount of a compound of formula ##STR50## wherein R 1  is hydrogen, loweralkyl, arylloweralkyl, a group of formula R 2  R 3  R 4  Si, a group of formula R 5  CO, a group of formula R 8  R 10  N(CHR 11 ) n  CO wherein n is 0 or 1, or OAr'; R 6  is hydrogen, hydroxyl, a group of formula OR 12 , a group of formula OCOR 13 , a group of formula OCONR 14  R 15 , or a group of formula OAr;   R 7  is defined as R 6 , or is a group of formula OCOR 16 , a group of formula OCONR 17  Z, a group of formula OCOAr', a group of formula OAr', a group of formula OCONR 17  Ar or a group of formula ##STR51## R 6  and R 7  taken together form a group of formula O--C(═S)--O;   R 9  is hydrogen;   or R 1  and R 9  maybe taken together to form a group of formula CO, or a group of formula SO or a group of formula CHNR 18  R 19  ;   R 2 , R 3 , and R 4  are the same or not all the same and each is loweralkyl;   R 5  is hydrogen or loweralkyl;   R 8 , R 10  and R 11  are the same or not all the same and each is hydrogen, loweralkyl or arylloweralkyl;   R 8  and R 10  taken together with the nitrogen atom to which they are attached form a group of formula ##STR52##  wherein X is CO, O, S, SO, SO 2 , a group of formula CHR 20  or a group of formula NR 21  ;   R 12  is loweralkyl or alkylaminoloweralkyl;   R 13  is hydrogen, straight or branched chain alkyl containing from 1 to 20 carbon atoms, --CH(OH)CH 2  OH, ##STR53## R 14  is hydrogen, loweralkyl, hydroxyloweralkyl, loweralkoxyloweralkyl, or a group of formula HOCH 2  CH(OH)CH 2  ;   R 15  is hydrogen, hydroxyl, loweralkoxy, loweralkyl, hydroxyloweralkyl, loweralkoxyloweralkyl, loweralkanoyl, loweralkanoylloweralkyl, a group of formula ##STR54##  wherein p is 1 or 2, a group of formula ##STR55##  a group of formula (CH 2 ) q  NR 22  R 23  wherein q is 0 or an integer from 2 to 6, a group of formula OR 24  or a group of formula OCOR 25  ;   R 16  is hydroxyloweralkyl, ##STR56##  wherein X is defined as above, a group of formula R 26  OCR 27  R 28  (CH 2 ) r  wherein r is 0, 1, 2 or 3, a group of formula R 29  R 30  N(CH 2 ) s  (CHR 31 )(CH 2 )s' wherein s and s' are the same or different and each is 0, 1 or 2 or a group of formula (CH 2 ) f  CO 2  H, wherein f is an integer from 0 to 5;   R 17  is hydrogen or loweralkyl;   R 18  and R 19  are the same or different and each is loweralkyl;   R 18  and R 19  taken together with the nitrogen atom to which they are attached form a group of formula ##STR57##  wherein L is O, S or CHR 20  ; R 20  is hydrogen or loweralkyl;   R 21  is hydrogen or loweralkyl;   R 22  and R 23  are the same or different and each is loweralkyl;   R 22  and R 23  taken together with the nitrogen atom to which they are attached form a group of formula ##STR58##  wherein X is defined as above; R 24  is hydrogen, loweralkyl, a group of formula (CH 2 ) q  NR 22  R 23  wherein R 22 , R 23  and q are as above;   R 25  is hydrogen, loweralkyl, lowercycloalkyl of 3 to 6 carbon atoms, haloloweralkenyl, loweralkanoylloweralkyl, loweralkoxyloweralkyl, loweralkoxycarbonylloweralkyl, loweralkylamino, lowerdialkylamino, a group of formula ##STR59##  wherein p is defined as above, a group of formula ##STR60##  a group of the formula (CH 2 ) q  NR 22  R 23  wherein R 22 , R 23  and q are as defined above, a group of formula ##STR61##  wherein X is as defined above and t is 0 or 1 or a group of formula (CH 2 ) u  N(R 33 )COR 34  wherein u is 1, 2 or 3;   R 26 , R 27  and R 28  are the same or not all the same and each is hydrogen or loweralkyl;   R 29  is hydrogen, loweralkyl or a group of formula R 35  CO;   R 30  is hydrogen or loweralkyl;   R 29  and R 30  taken together with the nitrogen atom to which they are attached form a group of formula ##STR62##  wherein X is defined above; R 31  is hydrogen, loweralkyl, arylloweralkyl or hydroxyl;   R 33 , R 34  and R 35  are the same or not all the same and each is hydrogen or loweralkyl;   Ar is phenyl, naphthyl, pyridinyl, pyridazinyl or pyrimidinyl, each of which is unsubstituted or mono- or poly-substituted by loweralkyl, halogen or nitro;   Ar' is phenyl, naphthyl, pyridinyl, pyridazinyl, pyrimidinyl, furanyl, oxazolyl, purinyl or thiazolyl, each of which is unsubstituted or mono- or poly-substituted by loweralkyl, halogen, nitro, or a group of formula NR 34'  R 35' , or phenyl, naphthyl, pyridinyl or pyrimidinyl, each of which is mono- or poly-substituted by a group of formula NR 34'  R 35' ,;   R 34'   and R 35'   are the same or different and each is hydrogen, loweralkyl or alkylaminoloweralkyl;   R 34'   and R 35'   taken together with the nitrogen atom to which they are attached form a group of formula ##STR63##  wherein M is NR 47'   O or CH 2  and y is 0, 1 or 2; Z is a group of formula (CH 2 ) v  NR 37  R 38  wherein v is an integer from 0 to 5, a group of formula N═CR 39  R 40  or a group of formula (CH 2 ) g  CO 2  H wherein g is an integer from 0 to 5;   Z and R 17  and the nitrogen atom to which they are attached form a group ##STR64##  wherein M is NR 47 , O or CH 2  and y is 0, 1 or 2; R 37  and R 38  are the same or different and each is hydrogen, loweralkyl or a group of formula COR 41  ;   R 37  and R 38  taken together with the nitrogen atom to which they are attached form a group of formula N X wherein X is defined as above;   R 39  is loweralkyl;   R 40  is loweralkyl, loweralkenyl, a group of formula ##STR65##  or a group of formula ##STR66## R 39  and R 40  taken together with the carbon atom to which they are attached form a group of formula ##STR67##  wherein W is O, a group of the formula NR 42 , or a group of formula CHR 43  ;   R 41  is loweralkyl or a group of formula (CH 2 ) x  NR 44  R 45  wherein x is an integer from 0 to 5;   R 42  is loweralkyl;   R 43  is hydrogen, loweralkyl or a group of formula OR 46  ;   R 44  and R 45  are the same or different and each is loweralkyl;   R 46  is loweralkyl;   R 47  is hydrogen, loweralkyl or (C═O)loweralkyl; and the optical and geometric isomers thereof, or a pharmaceutically acceptable salt thereof, provided:   (a) if R 6  is hydrogen, then R 7  is not hydrogen;   (b) if R 7  is hydrogen, then R 6  is not hydrogen; and   (c) if neither R 6  nor R 7  is hydrogen, then R 6  is OH, R 13  C(═O)O, a group of formula OR 12 , a group of formula OCONR 14  R 15  or a group of formula OAr, R 7  is ##STR68## or R 6  and R 7  taken together form a group of formula O--C(═S)--O.   
     
     
       33. A method according to claim 32 wherein the compound is 6-deoxy-7-desacetyl-7-(pyrimidin-2-yl)forskolin hydrochloride. 
     
     
       34. A cardiac failure treating composition comprising an inert adjuvant and an amount effective in treating cardiac failure of a compound of formula ##STR69## wherein R 1  is hydrogen, loweralkyl, arylloweralkyl, a group of formula R 2  R 3  R 4  Si, a group of formula R 5  CO, a group of formula R 8  R 10  N(CHR 11 ) n  CO wherein n is 0 or 1, or Ar'; R 6  is hydrogen, hydroxyl, a group of formula OR 12 , a group of formula OCOR 13 , a group of formula OCONR 14  R 15 , or a group of formula OAr;   R 7  is defined as R 6 , or is a group of formula OCOR 16 , a group of formula OCONR 17  Z, a group of formula OAr', a group of formula OCOAr', a group of formula OCONR 17  Ar or a group of formula ##STR70## R 6  and R 7  taken together form a group of formula O--C(═S)--O;   R 9  is hydrogen;   or R 1  and R 9  maybe taken together to form a group of formula CO, or a group of formula SO or a group of formula CHNR 18  R 19  ;   R 2 , R 3 , and R 4  are the same or not all the same and each is loweralkyl;   R 5  is hydrogen or loweralkyl;   R 8 , R 10  and R 11  are the same or not all the same and each is hydrogen, loweralkyl or arylloweralkyl;   R 8  and R 10  taken together with the nitrogen atom to which they are attached form a group of formula ##STR71## wherein X is CO, O, S, a group of formula CHR 20  or a group of formula NR 21  ;   R 12  is loweralkyl or alkylaminoloweralkyl;   R 13  is hydrogen, straight or branched chain alkyl containing from 1 to 20 carbon atoms, --CH(OH)CH 2  OH, ##STR72## R 14  is hydrogen, loweralkyl, hydroxyloweralkyl, loweralkoxyloweralkyl, or a group of formula HOCH 2  CH(OH)CH 2  ;   R 15  is hydrogen, hydroxyl, loweralkoxy, loweralkyl, hydroxyloweralkyl, loweralkoxyloweralkyl, loweralkanoyl, loweralkanoylloweralkyl, a group of formula ##STR73##  wherein p is 1 or 2, a group of formula ##STR74##  a group of formula (CH 2 ) q  NR 22  R 23  wherein q is an integer from 0 to 6, a group of formula OR 24  or a group of formula OCOR 25  ;   R 16  is hydroxyloweralkyl, ##STR75##  wherein X is defined as above, a group of formula R 26  OCR 27  R 28  (CH 2 ) r  wherein r is 0, 1, 2 or 3, a group of formula R 29  R 30  N(CH 2 ) s  (CHR 31 )(CH 2 ) s'   wherein s and s' are the same or different and each is 0, 1, or 2 or a group of formula (CH 2 ) f  CO 2  H wherein f is an integer from 0 to 5;   R 17  is hydrogen or loweralkyl;   R 18  and R 19  are the same or different and each is loweralkyl;   R 18  and R 19  taken together with the nitrogen atom to which they are attached form a group of formula ##STR76##  wherein L is O, S or CHR 20  ; R 20  is hydrogen or loweralkyl;   R 21  is hydrogen or loweralkyl;   R 22  and R 23  are the same or different and each is loweralkyl;   R 22  and R 23  taken together with the nitrogen atom to which they are attached form a group of formula ##STR77##  wherein X is defined as above; R 24  is hydrogen, loweralkyl, a group of formula (CH 2 ) q  NR 22  R 23  wherein R 22 , R 23  and q are as above;   R 25  is hydrogen, loweralkyl, lowercycloalkyl of 3 to 6 carbon atoms, haloloweralkenyl, loweralkanoylloweralkyl, loweralkoxyloweralkyl, loweralkoxycarbonylloweralkyl, loweralkylamino, lowerdialkylamino, a group of formula ##STR78##  wherein p is defined as above, a group of formula ##STR79##  a group of the formula (CH 2 ) q  NR 22  R 23  wherein R 22 , R 23  and q are as defined above, a group of formula ##STR80##  wherein X is as defined above and t is 0 or 1 or a group of formula (CH 2 ) u  N(R 33 )COR 34  wherein u is 1, 2 or 3;   R 26 , R 27  and R 28  are the same or not all the same and each is hydrogen or loweralkyl;   R 29  is hydrogen, loweralkyl or a group of formula R 35  CO;   R 30  is hydrogen or loweralkyl;   R 29  and R 30  taken together with the nitrogen atom to which they are attached form a group of formula ##STR81##  wherein X is defined above; R 31  is hydrogen, loweralkyl, arylloweralkyl or hydroxyl;   R 33  and R 34  are the same or different and each is hydrogen or loweralkyl;   Ar is phenyl, naphthyl, pyridinyl or pyrimidinyl, each of which is unsubstituted or mono- or poly-substituted by loweralkyl, halogen or nitro;   Ar' is phenyl, naphthyl, pyridinyl, pyridazinyl, pyrimidinyl, furanyl, oxazolyl, purinyl or thiazolyl, each of which is unsubstituted or mono- or poly-substituted by loweralkyl, halogen, nitro, or a group of formula NR 34'  R 35' , or phenyl, naphthyl, pyridinyl or pyrimidinyl, each of which is mono- or poly-substituted by a group of formula NR 34'  R 35' ,;   R 34'   and R 35'   are the same or different and each is hydrogen, loweralkyl or alkylaminoloweralkyl;   R 34'   and R 35'   taken together with the nitrogen atom to which they are attached form a group of formula ##STR82##  wherein M is NR 47 , O or CH 2  and y is 0, 1 or 2; Z is a group of formula (CH 2 ) v  NR 37  R 38  wherein v is 0 or an integer from 2 to 5, a group of formula (CH 2 ) f  CO 2  H wherein f is an integer from 0 to 5, a group of formula N═CR 39  R 40  or a group for formula (CH 2 ) g  CO 2  H wherein g is an integer from 0 to 5;   Z and R 17  and the nitrogen atom to which they attached form a group of formula ##STR83##  wherein M is NR 47 , O or CH 2  and y is 0, 1 or 2; R 37  and R 38  are the same or different and each is hydrogen, loweralkyl or a group of formula COR 40  ;   R 37  and R 38  taken together with the nitrogen atom to which they are attached form a group of formula ##STR84##  wherein X is defined as above; R 39  is loweralkyl;   R 40  is loweralkyl, loweralkenyl, a group of formula ##STR85##  or a group of formula ##STR86## R 39  and R 40  taken together with the carbon atom to which they are attached form a group of formula ##STR87##  wherein W is O, a group of the formula NR 42 , or a group of formula CHR 43  ;   R 41  is loweralkyl or a group of formula (CH 2 ) x  NR 44  R 45  wherein x is an integer from 0 to 5;   R 42  is loweralkyl;   R 43  is hydrogen, loweralkyl or a group of formula OR 46  ;   R 44  and R 45  are the same or different and each is loweralkyl;   R 46  is loweralkyl;   R 47  is hydrogen, loweralkyl or (C═O)loweralkyl; and   the optical and geometric isomers thereof, or a pharmaceutically acceptable salt thereof, provided:   (a) if R 6  is hydrogen, then R 7  is not hydrogen;   (b) if R 7  is hydrogen, then R 6  is not hydrogen; and   (c) if neither R 6  nor R 7  is hydrogen, then R 6  is OH, a group of formula OR 12 , a group of formula OCONR 14  R 15 , a group of formula OArR 13  C(═O)O, R 7  is ##STR88##  or R 6  and R 7  taken together form a group of formula O--C(═S)--O.   
     
     
       35. A composition according to claim 34 wherein the compound is 6-deoxy-7-desacetyl-7-(pyrimidin-2-yl)forskolin hydrochloride. 
     
     
       36. A pharmaceutical composition comprising an inert adjuvant and a pharmaceutically effective amount of a compound as claimed in claim 1. 
     
     
       37. A process for the preparation of a compound of formula ##STR89## wherein R 1  and R 9  are hydrogen, the optical and geometric isomers thereof, or a pharmaceutically acceptable salt thereof, which comprises: (a) contacting a compound of formula: ##STR90##  wherein R 18  and R 19  are the same or different and each is loweralkyl; R 18  and R 19  taken together with the nitrogen atom to which they are attached form a group of formula ##STR91##  wherein L is O, S or a group of formula CHR 20  ; R 20  is hydrogen or loweralkyl; with a compound of formula compound of formula ##STR92##  to provide a ##STR93## (b) contacting the product of step (a) with a organic or inorganic base to provide a compound of formula ##STR94## (c) contacting the product of step (b) with a radical initiator and a trialkyltin hydride to provide a compound of formula: ##STR95##  and (d) deacetalating the product of step (c).     
     
     
       38. The process of claim 37 wherein said base is selected from the group consisting of sodium hydroxide, sodium carbonate and an alkali metal bis(triloweralkylsilyl)amide. 
     
     
       39. The process of claim 38 wherein said base is lithium bis(trimethylsilyl)amide. 
     
     
       40. The process of claim 37 wherein said trialkyltin hydride is tri-n-butyltin hydride. 
     
     
       41. The process of claim 37, wherein a catalyst is employed in step (a). 
     
     
       42. The process of claim 41, wherein said catalyst is 4-dimethylaminopyridine or 4-pyrrolidinopyridine. 
     
     
       43. The process of claim 37 wherein the product of step (c) is deacetalated by treatment with a mixture of an alkanol and water, a mixture of an alkanol, water and an alkanoic acid or with a mixture of an alkanol, water and a mineral acid. 
     
     
       44. The process of claim 37 wherein contact in step (a) is conducted at a temperature between about 25° and 120° C. 
     
     
       45. The process of claim 44 wherein said temperature is between about 60° and 65° C. 
     
     
       46. The process of claim 37 wherein the contact in step (c) is conducted at a temperature between about 90° and 130° C. 
     
     
       47. The process of claim 46 wherein said temperature is between about 100° and 115° C. 
     
     
       48. The process of claim 37 which further comprises: (i) contacting the product of step (c) with a compound of formula R 7  --Hal wherein R 7  is phenyl, naphthyl, pyridazinyl furanyl, oxazolyl, thiazolyl, pyridinyl, pyrimidinyl or purinyl, each of which is unsubstituted or mono- or polysubstituted by loweralkyl, halogen or nitro and Hal is halogen, in the presence of a metal alkoxide or metal bis(trialkylsilylamide) to provide a compound of formula ##STR96##  and (ii) deacetalating the product of step (i) to provide a compound of formula ##STR97##  and the optical and geometric isomers thereof, or a pharmaceutically acceptable salt thereof.   
     
     
       49. The process of claim 48 wherein the metal alkoxide is potassium t-butoxide or the metal bis(trialkylsilylamide) is potassium bis (trimethylsilylamide). 
     
     
       50. The process of claim 48 wherein the product of step (i) is deacetalated by treatment with a mixture of an alkanol and water, a mixture of an alkanol, water and an alkanoic acid or a mixture of an alkanol, water and a mineral acid. 
     
     
       51. The process of claim 48 which further comprises: (a) contacting the product of step (ii) wherein R 7  is phenyl, naphthyl, furanyl, oxazolyl, thiazolyl, pyridinyl, pyrimidinyl, pyridazinyl or purinyl, each of which is mono- or polysubstituted by halogen, with a compound of formula HNR 34'   and R 35'   wherein R 34'   and R 35'   are the same or different and each is hydrogen, loweralkyl, or alkylaminoloweralkyl and R 34'   and R 35'   taken together with the nitrogen atom to which they are attached form a group of formula ##STR98##  wherein Q is NR 48 , O or CH 2 , y is 0, 1 or 2 and R 48  is loweralkyl, (C═O)loweralkyl or (C═O)Ophenyl, to provide a compound of formula ##STR99##  wherein R 7 , is phenyl, naphthyl, furanyl, oxazolyl, thiazolyl, pyridinyl, pyrimidinyl, pyridazinyl or purinyl, each of which is mono or polysubstituted by NR 34'  R 35'  ; and   (b) deacetalating the product of step (a).   
     
     
       52. The process of claim 51 wherein the product of step (ii) is contacted with the compound of formula HNR 34'  R 35'   in the presence of a mineral acid.